Background/Purpose: We have previously reported that patients with gout have impaired vascular endothelial and smooth muscle responsiveness, but whether initiating appropriate gout therapy ameliorates these impairments, or improves baseline inflammatory status, has not been determined.

Methods: We performed an observational pilot study to assess whether initiating gout therapy improves vascular function as well as markers of inflammation. Subjects meeting ACR classification and treatment criteria for gout, but not actively receiving gout medications, were enrolled. Baseline demographics were obtained. Subjects were given colchicine daily for 6 weeks, followed by addition of urate-lowering therapy (ULT; allopurinol or febuxostat at the discretion of the treating physician) and titration to a target serum urate (sUA) of <6.0 mg/dL, or <5.0 mg/dL for subjects with tophi.  hsCRP was measured pre and post the colchicine-only period, and 4 weeks after achieving target sUA. Endothelial responsiveness was assessed using ultrasound as brachial artery dilation in response to application/release of a blood pressure cuff (flow-mediated dilation, FMD). Vascular smooth muscle function was assessed as brachial artery dilation in response to sublingual nitroglycerine (0.4 mg) administration (nitrate-mediated dilation, NMD).

Results:   34 male subjects were enrolled, and 28 completed all study phases.  Mean age was 57.9 years, and mean BMI 30.3. Co-morbidities included hypertension (HTN, 71%); hyperlipidemia (HL, 50%); coronary artery disease (CAD, 21%); chronic kidney disease (14.7%) and diabetes (6%).  26% were current smokers. Mean baseline sUA was 9.1 mg/dL, and declined after ULT (p baseline vs post-ULT, <0.001) (Table). Baseline hsCRP was elevated, and FMD and NMD reduced, vs healthy controls. We observed a pattern of improvement in hsCRP and FMD after colchicine treatment, and further improvement after ULT initiation (mostly allopurinol), but no NMD improvement. Whereas subjects without comorbidities (HTN, HL, CAD and/or BMI>30) experienced improvements in both hsCRP and FMD, subjects with individual or multiple CV co-morbidities experienced improvement in hsCRP but not FMD. In contrast, smokers experienced improvement in both inflammatory and endothelial parameters in response to treatment.

Conclusion: Initiating colchicine prophylaxis and ULT in gout patients reduces systemic inflammation.  Improvement in endothelial function is also observed, but patients with established CV comorbidities may be resistant to endothelial improvement.  These data suggest that proper gout treatment may have direct benefit in reducing CV risk. Whether longer term treatment could have additional impact, particularly on patients with established CV comorbidities, remains to be determined.